Genetic Determinants of Kawasaki Disease

Genetic Determinants of Kawasaki Disease for Susceptibility and Outcome

Kawasaki disease (KD) is an acute self-limited vasculitis of infancy and early childhood. Most patients recover without sequelae although the inflammatory process causes permanent damage to the coronary arteries in 20-25% of untreated children. An infectious aetiology is suspected, but the causative agent has not been identified. The investigators aim to identify the genes underlying both susceptibility to Kawasaki disease, and the development of coronary artery aneurysms.

Study Overview

• Status: Active, not recruiting
• Conditions: Kawasaki Disease; Atypical Kawasaki Disease

Detailed Description

The problem to be addressed;

Kawasaki disease is now the most common cause of acquired heart disease in children in Japan and North America. Kawasaki disease arises when genetically predisposed children encounter an as yet unidentified infectious agent which may cause only mild illness or no illness at all in children without the genetic predisposition. Other children may suffer permanent damage to the coronary arteries. Identification of the genes involved will help to improve understanding of the disease, and the development of better treatments.

Objective

The investigators aim to identify the genes underlying both susceptibility to Kawasaki disease, and the development of coronary artery aneurysms.

Design

The study will recruit nuclear families (affected child and their biological parents) through participating NHS hospitals or through the records of the UK Kawasaki Support Group.

Study size

400 affected children and both biological parents (i.e. 1200 participants)

Procedures

Informed consent using age appropriate patient/parent/guardian information sheets will be taken from parents (or from children aged 16 and over), assent will be taken from the child under the age of 16 (if appropriate). Children recruited during the acute illness; routine clinical and laboratory data and research samples (blood, urine, throat swab). Children recruited retrospectively; study questionnaire (completed by parents), saliva samples.Saliva samples from parents

• Study Type: Observational
• Enrollment (Actual): 1379

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom, W2 1PG
    • Imperial College London

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Children under the care of consultant in hospital for Kawasaki disease, families who are members of the UK Kawasaki Support Group

Description

Inclusion Criteria:

• Affected children will be recruited if the treating clinician has made a diagnosis of possible Kawasaki disease (even if they do not fulfil the criteria below for Kawasaki disease).

The current standard diagnostic criteria for KD (Circulation 2001 103 335-336 doi: 10.1161/01.CIR 103.2.335) are:

The presence of fever for at least five days plus four of the following criteria:

1. Changes in the peripheral extremities Acute: erythema and oedema of hands and feet Convalescent: membranous desquamation of fingertips
2. Polymorphous exanthema
3. Bilateral painless bulbar conjunctival injection without exudate
4. Changes in lips and oral cavity: erythema and cracking of lips, strawberry tongue, diffuse injection of oral and pharyngeal mucosae
5. Cervical lymphadenopathy (>1.5cm diameter), usually unilateral Patients meeting not all of these criteria may meet the criteria for atypical Kawasaki disease, ie. if they have fever and two or three of the above criteria and elevation of CRP or echocardiographic evidence of coronary artery dilatation.

Parents of affected child must be biological parents.

Exclusion Criteria:

• children who do not have a diagnosis of possible Kawasaki disease

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Other

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Kawasaki disease; Kawasaki disease affected children
parent of Kawasaki disease affected child

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Susceptibility of coronary artery aneurysms for Kawasaki patients	Identification of genes that are associated with susceptibility of coronary artery aneurysms	end date; 30 December 2022

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease severity for Kawasaki patients	Identification of genes that are associated with disease severity	end date; 30 December 2022

Collaborators and Investigators

• Sponsor: Imperial College London
• Collaborators: Cambridge University Hospitals NHS Foundation Trust; Guy's and St Thomas' NHS Foundation Trust; University Hospital Birmingham NHS Foundation Trust; University Hospitals Bristol and Weston NHS Foundation Trust; Imperial College Healthcare NHS Trust; Great Ormond Street Hospital for Children NHS Foundation Trust; Tameside Hospital NHS Foundation Trust; University Hospitals Coventry and Warwickshire NHS Trust; St. George's Hospital, London; South Tees Hospitals NHS Foundation Trust; Sheffield Children's NHS Foundation Trust; Birmingham Children's Hospital; Bradford Royal Infirmary; Royal Alexandra Children's Hospital; University Hospitals of North Midlands NHS Trust; Leeds General Infirmary; East Suffolk and North Essex NHS Foundation Trust; Royal Cornwall Hospitals Trust; Royal Bolton Hospital NHS Foundation Trust; Royal Oldham Hospital; Northwick Park Hospital; Burton Hospitals NHS Foundation Trust; Kingston Hospital NHS Trust; University Hospitals of Morecambe Bay NHS Trust; Darlington Memorial Hospital; York Teaching Hospitals NHS Foundation Trust; UK Kawasaki Support Group; Shrewsbury and Telford Hospitals NHS Trust; New Cross Hospital; Torbay Hospital; Peterborough City Hospital; University Hospital of North Tees; Wye Valley NHS Trust; Calderdale and Huddersfield NHS Foundation Trust; St. Richard's Hospital; Pinderfields General Hospital; Worthing Hospital; Airedale General Hospital; West Middlesex Hospital; Royal Albert Edward Infirmary; Macclesfield District General Hospital; Stepping Hill Hospital; North Manchester General Hospital; East Surrey Hospital
• Investigators: Study Chair: Professor M Levin, Imperial College London

Study record dates

Study Major Dates

• Study Start (Actual): February 25, 2013
• Primary Completion (Anticipated): December 30, 2022
• Study Completion (Anticipated): December 30, 2022

Study Registration Dates

• First Submitted: March 1, 2019
• First Submitted That Met QC Criteria: March 1, 2019
• First Posted (Actual): March 4, 2019

Study Record Updates

• Last Update Posted (Actual): November 17, 2022
• Last Update Submitted That Met QC Criteria: November 15, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Keywords: Kawasaki Disease
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Skin Diseases; Lymphatic Diseases; Vasculitis; Skin Diseases, Vascular; Mucocutaneous Lymph Node Syndrome
• Other Study ID Numbers: 13SM0678

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No